资源环境科技发展态势分析平台

Strain engineering is a powerful tool with which to enhance semiconductor device performance(1,2). Halide perovskites have shown great promise in device applications owing to their remarkable electronic and optoelectronic properties(3-5). Although applying strain to halide perovskites has been frequently attempted, including using hydrostatic pressurization(6-8), electrostriction(9), annealing(10-12), van der Waals force(13), thermal expansion mismatch(14), and heat-induced substrate phase transition(15), the controllable and device-compatible strain engineering of halide perovskites by chemical epitaxy remains a challenge, owing to the absence of suitable lattice-mismatched epitaxial substrates. Here we report the strained epitaxial growth of halide perovskite single-crystal thin films on lattice-mismatched halide perovskite substrates. We investigated strain engineering of a-formamidinium lead iodide (alpha-FAPbI(3)) using both experimental techniques and theoretical calculations. By tailoring the substrate composition-and therefore its lattice parameter-a compressive strain as high as 2.4 per cent is applied to the epitaxial alpha-FAPbI(3) thin film. We demonstrate that this strain effectively changes the crystal structure, reduces the bandgap and increases the hole mobility of alpha-FAPbI(3). Strained epitaxy is also shown to have a substantial stabilization effect on the alpha-FAPbI(3) phase owing to the synergistic effects of epitaxial stabilization and strain neutralization. As an example, strain engineering is applied to enhance the performance of an alpha-FAPbI(3)-based photodetector.

Metabolites that are elevated in tumours inhibit the lysine demethylase KDM4B, resulting in aberrant hypermethylation of histone 3 lysine 9 and decreased homology-dependent DNA repair.

Deregulation of metabolism and disruption of genome integrity are hallmarks of cancer(1). Increased levels of the metabolites 2-hydroxyglutarate, succinate and fumarate occur in human malignancies owing to somatic mutations in the isocitrate dehydrogenase-1 or -2 (IDH1 or IDH2) genes, or germline mutations in the fumarate hydratase (FH) and succinate dehydrogenase genes (SDHA, SDHB, SDHC and SDHD), respectively(2-4). Recent work has made an unexpected connection between these metabolites and DNA repair by showing that they suppress the pathway of homology-dependent repair (HDR)(5,6) and confer an exquisite sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP) that are being tested in clinical trials. However, the mechanism by which these oncometabolites inhibit HDR remains poorly understood. Here we determine the pathway by which these metabolites disrupt DNA repair. We show that oncometabolite-induced inhibition of the lysine demethylase KDM4B results in aberrant hypermethylation of histone 3 lysine 9 (H3K9) at loci surrounding DNA breaks, masking a local H3K9 trimethylation signal that is essential for the proper execution of HDR. Consequently, recruitment of TIP60 and ATM, two key proximal HDR factors, is substantially impaired at DNA breaks, with reduced end resection and diminished recruitment of downstream repair factors. These findings provide a mechanistic basis for oncometabolite-induced HDR suppression and may guide effective strategies to exploit these defects for therapeutic gain.

The structure of human diacylglycerol O-acyltransferase 1, a membrane protein that synthesizes triacylglycerides, is solved with cryo-electron microscopy, providing insight into its function and mechanism of enzymatic activity.

Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans(1). DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins(2,3). How human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions is unknown. The absence of three-dimensional structures also hampers rational targeting of DGAT1 for therapeutic purposes. Here we present the cryo-electron microscopy structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold that we name the MBOAT fold. The MBOAT fold in DGAT1 forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 can exist as either a homodimer or a homotetramer and the two forms have similar enzymatic activity. The N terminus of DGAT1 interacts with the neighbouring protomer and these interactions are required for enzymatic activity.